OsHV-1 currently causes mass mort alities in Pacific oysters in Tomales Bay, California, USA, and a virulent microvariant of this virus has recently been detected in San Diego Bay, California, USA . Selective breeding of oysters for disease tolerance is one of the best mitigation strategies available for reducing the impact of OsHV-1 once it has become established in a bay. Selective breeding conducted by the Molluscan Broodstock Program (MBP), a Pacific oyster breeding program at the Hatfield Marine Science Center (Newport, Oregon, USA), has increased the likelihood of survival to OsHV-1 (Tomales Bay variant) in the MBP oyster breeding population by 21 percentage points. Understanding the causal genes controlling OsHV-1 tolerance can make selection more accurate and increase our understanding of the mechanisms controlling innate immunity in oysters. Conducting a genome-wide association study (GWAS) in the MBP breeding population using SNPs from next-generation sequencing (NGS) data, we found a region on chromosome 8 that was significantly associated with OsHV-1 tolerance. Furthermore, we found that this region is significantly positively correlated with the gene expression levels of two viral innate immunity genes . Family-based QTL analyses replicated the population-based results but also revealed the existence of family-specific genomic regions that are responsible for OsHV-1 tolerance. This suggests that OsHV-1 tolerance in Tomales Bay is controlled by multiple genes possibly active in different innate immune pathways. Selecting for diverse innate immune pathways in oysters can ensure that tolerance to OsHV-1 stays durable against evolution by OsHV-1.